Study of clinical experience with different approaches to controlled ovarian hyperstimulation: a focus on safety and efficacy.

OBJECTIVES: Current retrospective cohort study analyses clinical database records of 4792 assisted reproduction procedures to assess the significance of target effectiveness endpoints from a safety perspective. METHODS: Stimulation protocols with urinary, recombinant or combination of both types gonadotrophin preparations are compared according to the following primary endpoints: incidence of ovarian hyperstimulation syndrome (OHSS), cycle cancellation, follicle count, induced estradiol values, clinical pregnancy achieved and cycles reached embryo transfer/freezing. We have investigated the incidence of cases evaluated as 'risky for OHSS' by secondary efficacy endpoints (exogenous gonadotrophin exposure, luteinising hormone and progesterone values, oocyte yield, eggs with normal maturation). The following statistical methods were applied: descriptive statistics, Mann-Whitney U test, Kruskal-Wallis test, Pearson chi-square test, Fisher's exact test, binary logistic regression. RESULTS: Only 16 cases (0.42%) of moderate and delayed OHSS were established. Three hundred and seven (8.6%) stimulation cycles have been cancelled, principally among urinary protocols. Although the clinical pregnancy rate does not differ significantly in compared groups, punctured follicle count, oocyte yield and progesterone level were higher for recombinant preparations, followed by combined and urinary protocols. Follicle count, mean estradiol and luteinising hormone levels are within the 'safe window' for all investigated groups, associated with minimised risk of stimulation cancellation. The mean follicle-stimulating hormone (FSH) dose was highest in urinary protocols at the same duration of stimulation compared with recombinant products. The younger age, bigger follicle count, oocytes yield, mature oocytes count, percentage of fertilised oocytes, more embryos transferred and the later day of embryo transfer are critical for both assisted reproduction techniques (ART) success rate and the safety profile of sterility treatment. CONCLUSIONS: Safety surveillance of ART exceeds the incidence of OHSS. Suboptimal effectiveness of stimulation protocols may also jeopardise the well-being of ART patients. Gonadotrophin exposure, induced values of sex hormones, and quantity and quality of extracted oocytes should be considered to minimise any unintended suffering of treated couples.

Physicians' knowledge and attitude towards adverse event reporting system and result to intervention--randomized nested trial among Bulgarian physicians.

AIM: To identify the factors that influence physicians' under-reporting in Bulgaria and their attitude towards adverse event reporting system and to estimate the role of self-education by providing educational materials. METHODS: A randomized nested trial among physicians-general practitioners and specialists in Bulgaria was conducted by a validated questionnaire in order to evaluate their knowledge and attitude towards adverse event reporting system. One month after the intervention the participants were re-visited and were asked to answer the same questions again in order to estimate the change in their knowledge and attitude towards pharmacovigilance system and to obtain their evaluation for the materials provided. RESULTS: The response rate was 91. Fifty seven (46.3%) physicians were not familiar with the pharmacovigilance system. The most common reason for non-reporting adverse drug reactions (ADRs) was uncertainty concerning the relationship between the suspected drug and ADRs, the ADRs were already known and the fact that the physician was not aware where they should report. Although 103 (83.7%) respondents in the entry survey and by 102 (82.9%) of those participating in the exit survey consider ADRs reporting as their obligation (p more than 0.05), only 50 (40.7%) and 31 (25.2%), respectively answered that they had ever reported ADRs; 109 (88.6%) of the surveyed physicians assessed the provided educational materials as useful for them. CONCLUSION: The physicians in Bulgaria have poor knowledge for the pharmacovigilance system; however self-education leads to a better knowledge and positive attitude towards ADRs reporting system. National drug regulatory authority should play a more active role in improving physicians' adherence to the ADRs reporting systems and the developed educational pack can be used in nationwide campaign.